Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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Genetic variations affecting response of radiotherapy

  • Choi, Eun Kyung (Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2022.01.10
  • Accepted : 2022.04.30
  • Published : 2022.06.30
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Abstract

Radiation therapy (RT) is a very important treatment for cancer that irradiates a large amount of radiation to lead cancer cells and tissues to death. The progression of RT in the aspect of personalized medicine has greatly advanced over the past few decades in the field of technical precision responding anatomical characteristics of each patient. However, the consideration of biological heterogeneity that makes different effect in individual patients has not actually applied to clinical practice. There have been numerous discovery and validation of biomarkers that can be applied to improve the efficiency of radiotherapy, among which those related to genomic information are very promising developments. These genome-based biomarkers can be applied to identify patients who can benefit most from altering their therapeutic dose and to select the best chemotherapy improving sensitivity to radiotherapy. The genomics-based biomarkers in radiation oncology focus on mutational changes, particularly oncogenes and DNA damage response pathways. Although few have translated into clinically viable tools, there are many promising candidates in this field. In this review the prominent mutation-based biomarkers and their potential for clinical translation will be discussed.

Keywords

Acknowledgement

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HI20C1586), and by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2019R1A2C2009183).

References

  1. Krzyszczyk P, Acevedo A, Davidoff EJ, Timmins LM, Marrero-Berrios I, Patel M, et al. The growing role of precision and personalized medicine for cancer treatment. Technology (Singap World Sci) 2018;6:79-100. https://doi.org/10.1142/s2339547818300020
  2. Martin OA, Martin RF. Cancer radiotherapy: understanding the price of tumor eradication. Front Cell Dev Biol 2020;8:261. https://doi.org/10.3389/fcell.2020.00261
  3. Franzone P, Fiorentino A, Barra S, Cante D, Masini L, Cazzulo E, et al. Image-guided radiation therapy (IGRT): practical recommendations of Italian Association of Radiation Oncology (AIRO). Radiol Med 2016;121:958-65. https://doi.org/10.1007/s11547-016-0674-x
  4. Sheng Y, Zhang J, Ge Y, Li X, Wang W, Stephens H, et al. Artificial intelligence applications in intensity modulated radiation treatment planning: an overview. Quant Imaging Med Surg 2021;11:4859-80. https://doi.org/10.21037/qims-21-208
  5. Glide-Hurst CK, Chetty IJ. Improving radiotherapy planning, delivery accuracy, and normal tissue sparing using cutting edge technologies. J Thorac Dis 2014;6:303-18.
  6. Gong L, Zhang Y, Liu C, Zhang M, Han S. Application of radiosensitizers in cancer radiotherapy. Int J Nanomedicine 2021;16:1083-102. Erratum in: Int J Nanomedicine 2021;16:8139-40. https://doi.org/10.2147/IJN.S290438
  7. Scarborough JA, Scott JG. Translation of precision medicine research into biomarker-informed care in radiation oncology. Semin Radiat Oncol 2022;32:42-53. https://doi.org/10.1016/j.semradonc.2021.09.001
  8. Huang RX, Zhou PK. DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. Signal Transduct Target Ther 2020;5:60. https://doi.org/10.1038/s41392-020-0150-x
  9. Weber AM, Ryan AJ. ATM and ATR as therapeutic targets in cancer. Pharmacol Ther 2015;149:124-38. https://doi.org/10.1016/j.pharmthera.2014.12.001
  10. Pitter KL, Casey DL, Lu YC, Hannum M, Zhang Z, Song X, et al. Pathogenic ATM mutations in cancer and a genetic basis for radiotherapeutic efficacy. J Natl Cancer Inst 2021;113:266-73. https://doi.org/10.1093/jnci/djaa095
  11. Sundar R, Brown J, Ingles Russo A, Yap TA. Targeting ATR in cancer medicine. Curr Probl Cancer 2017;41:302-15. https://doi.org/10.1016/j.currproblcancer.2017.05.002
  12. Vendetti FP, Lau A, Schamus S, Conrads TP, O'Connor MJ, Bakkenist CJ. The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo. Oncotarget 2015;6:44289-305. https://doi.org/10.18632/oncotarget.6247
  13. Lloyd RL, Wijnhoven PWG, Ramos-Montoya A, Wilson Z, Illuzzi G, Falenta K, et al. Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM-deficient cancer cells. Oncogene 2020;39:4869-83. https://doi.org/10.1038/s41388-020-1328-y
  14. Min A, Im SA, Jang H, Kim S, Lee M, Kim DK, et al. AZD6738, a novel oral inhibitor of ATR, induces synthetic lethality with ATM deficiency in gastric cancer cells. Mol Cancer Ther 2017;16:566-77. https://doi.org/10.1158/1535-7163.MCT-16-0378
  15. Dunlop CR, Wallez Y, Johnson TI, Bernaldo de Quiros Fernandez S, Durant ST, Cadogan EB, et al. Complete loss of ATM function augments replication catastrophe induced by ATR inhibition and gemcitabine in pancreatic cancer models. Br J Cancer 2020;123:1424-36. https://doi.org/10.1038/s41416-020-1016-2
  16. Lee JM, Ledermann JA, Kohn EC. PARP inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol 2014;25:32-40. https://doi.org/10.1093/annonc/mdt384
  17. Dziadkowiec KN, Gasiorowska E, Nowak-Markwitz E, Jankowska A. PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting. Prz Menopauzalny 2016;15:215-9.
  18. Cojocaru E, Parkinson CA, Brenton JD. Personalising treatment for high-grade serous ovarian carcinoma. Clin Oncol (R Coll Radiol) 2018;30:515-24. https://doi.org/10.1016/j.clon.2018.05.008
  19. Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys 2004;59(2 Suppl):21-6. https://doi.org/10.1016/j.ijrobp.2003.11.041
  20. Baumann M, Krause M, Overgaard J, Debus J, Bentzen SM, Daartz J, et al. Radiation oncology in the era of precision medicine. Nat Rev Cancer 2016;16:234-49. https://doi.org/10.1038/nrc.2016.18
  21. Kirsch DG, Diehn M, Kesarwala AH, Maity A, Morgan MA, Schwarz JK, et al. The future of radiobiology. J Natl Cancer Inst 2018;110:329-40. https://doi.org/10.1093/jnci/djx231
  22. Zheng DJ, Yu GH, Gao JF, Gu JD. Concomitant EGFR inhibitors combined with radiation for treatment of non-small cell lung carcinoma. Asian Pac J Cancer Prev 2013;14:4485-94. https://doi.org/10.7314/APJCP.2013.14.8.4485
  23. Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T, et al.; De-ESCALaTE HPV Trial Group. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet 2019;393:51-60. https://doi.org/10.1016/S0140-6736(18)32752-1
  24. Stokes WA, Sumner WA, Breggren KL, Rathbun JT, Raben D, McDermott JD, et al. A comparison of concurrent cisplatin versus cetuximab with radiotherapy in locally-advanced head and neck cancer: a biinstitutional analysis. Rep Pract Oncol Radiother 2017;22:389-95. https://doi.org/10.1016/j.rpor.2017.07.003
  25. Rivera F, Garcia-Castano A, Vega N, Vega-Villegas ME, Gutierrez-Sanz L. Cetuximab in metastatic or recurrent head and neck cancer: the EXTREME trial. Expert Rev Anticancer Ther 2009;9:1421-8. https://doi.org/10.1586/era.09.113
  26. Burmer GC, Loeb LA. Mutations in the KRAS2 oncogene during progressive stages of human colon carcinoma. Proc Natl Acad Sci U S A 1989;86:2403-7. https://doi.org/10.1073/pnas.86.7.2403
  27. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant cK-ras genes. Cell 1988;53:549-54. https://doi.org/10.1016/0092-8674(88)90571-5
  28. Tam IY, Chung LP, Suen WS, Wang E, Wong MC, Ho KK, et al. Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res 2006;12:1647-53. https://doi.org/10.1158/1078-0432.ccr-05-1981
  29. Liu P, Wang Y, Li X. Targeting the untargetable KRAS in cancer therapy. Acta Pharm Sin B 2019;9:871-9. https://doi.org/10.1016/j.apsb.2019.03.002
  30. Mak RH, Hermann G, Lewis JH, Aerts HJ, Baldini EH, Chen AB, et al. Outcomes by tumor histology and KRAS mutation status after lung stereotactic body radiation therapy for early-stage non-small-cell lung cancer. Clin Lung Cancer 2015;16:24-32. https://doi.org/10.1016/j.cllc.2014.09.005
  31. Cassidy RJ, Zhang X, Patel PR, Shelton JW, Escott CE, Sica GL, et al. Next-generation sequencing and clinical outcomes of patients with lung adenocarcinoma treated with stereotactic body radiotherapy. Cancer 2017;123:3681-90. https://doi.org/10.1002/cncr.30794
  32. Kamran SC, Lennerz JK, Margolis CA, Liu D, Reardon B, Wankowicz SA, et al. Integrative molecular characterization of resistance to neoadjuvant chemoradiation in rectal cancer. Clin Cancer Res 2019;25:5561-71. https://doi.org/10.1158/1078-0432.ccr-19-0908
  33. Chow OS, Kuk D, Keskin M, Smith JJ, Camacho N, Pelossof R, et al. KRAS and combined KRAS/TP53 mutations in locally advanced rectal cancer are independently associated with decreased response to neoadjuvant therapy. Ann Surg Oncol 2016;23:2548-55. https://doi.org/10.1245/s10434-016-5205-4
  34. Hong TS, Wo JY, Borger DR, Yeap BY, McDonnell EI, Willers H, et al. Phase II study of proton-based stereotactic body radiation therapy for liver metastases: importance of tumor genotype. J Natl Cancer Inst 2017;109:djx031.
  35. Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med 2020;383:1207-17. https://doi.org/10.1056/NEJMoa1917239
  36. Lin SH, Zhang J, Giri U, Stephan C, Sobieski M, Zhong L, et al. A high content clonogenic survival drug screen identifies MEK inhibitors as potent radiation sensitizers for KRAS mutant non-small-cell lung cancer. J Thorac Oncol 2014;9:965-73. https://doi.org/10.1097/jto.0000000000000199
  37. Wang Y, Li N, Jiang W, Deng W, Ye R, Xu C, et al. Mutant LKB1 confers enhanced radiosensitization in combination with trametinib in KRAS-mutant non-small cell lung cancer. Clin Cancer Res 2018;24:5744-56. https://doi.org/10.1158/1078-0432.CCR-18-1489
  38. Hong TS, Wo JYL, Ryan DP, Zheng H, Borger DR, Kwak EL, et al. Phase Ib study of neoadjuvant chemoradiation (CRT) with midostaurin, 5-fluorouracil (5-FU) and radiation (XRT) for locally advanced rectal cancer: sensitization of RAS mutant tumors. J Clin Oncol 2018;15 Suppl:e15674.
  39. Chowdhary M, Patel KR, Danish HH, Lawson DH, Khan MK. BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy. Onco Targets Ther 2016;9:7149-59. https://doi.org/10.2147/OTT.S119428
  40. Zaman A, Wu W, Bivona TG. Targeting oncogenic BRAF: past, present, and future. Cancers (Basel) 2019;11:1197. https://doi.org/10.3390/cancers11081197
  41. Ascierto PA, Kirkwood JM, Grob JJ, Simeone E, Grimaldi AM, Maio M, et al. The role of BRAF V600 mutation in melanoma. J Transl Med 2012;10:85. https://doi.org/10.1186/1479-5876-10-85
  42. Jin Z, Sinicrope FA. Advances in the therapy of BRAFV600E metastatic colorectal cancer. Expert Rev Anticancer Ther 2019;19:823-9. https://doi.org/10.1080/14737140.2019.1661778
  43. Maraka S, Janku F. BRAF alterations in primary brain tumors. Discov Med 2018;26:51-60.
  44. O'Leary CG, Andelkovic V, Ladwa R, Pavlakis N, Zhou C, Hirsch F, et al. Targeting BRAF mutations in non-small cell lung cancer. Transl Lung Cancer Res 2019;8:1119-24. https://doi.org/10.21037/tlcr.2019.10.22
  45. Gopal P, Abazeed M. High-throughput phenotyping of BRAF mutations reveals categories of mutations that confer resistance to radiation. IJROBP 2017;99:E591.
  46. Zahnreich S, Mayer A, Loquai C, Grabbe S, Schmidberger H. Radiotherapy with BRAF inhibitor therapy for melanoma: progress and possibilities. Future Oncol 2016;12:95-106. https://doi.org/10.2217/fon.15.297
  47. Sambade MJ, Peters EC, Thomas NE, Kaufmann WK, Kimple RJ, Shields JM. Melanoma cells show a heterogeneous range of sensitivity to ionizing radiation and are radiosensitized by inhibition of BRAF with PLX-4032. Radiother Oncol 2011;98:394-9. https://doi.org/10.1016/j.radonc.2010.12.017
  48. Hecht M, Zimmer L, Loquai C, Weishaupt C, Gutzmer R, Schuster B, et al. Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients. Ann Oncol 2015;26:1238-44. https://doi.org/10.1093/annonc/mdv139
  49. Anker CJ, Grossmann KF, Atkins MB, Suneja G, Tarhini AA, Kirkwood JM. Avoiding severe toxicity from combined BRAF inhibitor and radiation treatment: consensus guidelines from the Eastern Cooperative Oncology Group (ECOG). Int J Radiat Oncol Biol Phys 2016;95:632-46. Erratum in: Int J Radiat Oncol Biol Phys 2016;96:486. https://doi.org/10.1016/j.ijrobp.2016.01.038
  50. Patel KR, Chowdhary M, Switchenko JM, Kudchadkar R, Lawson DH, Cassidy RJ, et al. BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis. Melanoma Res 2016;26:387-94. https://doi.org/10.1097/CMR.0000000000000268
  51. Hecht M, Meier F, Zimmer L, Polat B, Loquai C, Weishaupt C, et al. Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients. Br J Cancer 2018;118:785-92. https://doi.org/10.1038/bjc.2017.489